Pediatric PSC A children s tale
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- Gervase Henderson
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1 Pediatric PSC A children s tale September 8 th PSC Partners seeking a cure Tamir Miloh Assistant Professor Pediatric Hepatology Mount Sinai Hospital, NY
2 Incidence Primary Sclerosing Cholangitis (PSC) ; rare progressive cholestatic disease. In children the incidence rate is 0.23/100,000 compared with 1.11/100,000 in adults. Median age of diagnosis in adults is 41 yr vs yr in children. More prevalent in male 3;1 and in Caucasians
3 Genetics PSC was found in 0.5% (4-fold increased risk) among first-degree relatives of patients with PSC The occurrence of UC among firstdegree relatives of patients with PSC was 0.9%
4 PSC and IBD 80% have IBD (UC and Crohn s colitis) 5% of IBD have PSC Either may precede No correlation between the severity of PSC and IBD More quiescent colitis and found on screening Annual surveillance colonoscopy for CA not required in children
5 Other associations Neonatal PSC Immunodeficiency Langerhans cell histiocytosis Cystic Fibrosis Overlap syndrome; Autoimmune hepatitis Other autoimmune disease, Autoimmune pancreatitis
6 Clinical Manifestations % asymptomatic at presentation Itching Jaundice (less common than adults) Abdominal pain Fatigue and weight loss Bone loss Acute presentation is rare Fever and acute cholangitis 10% - 15%
7 Physical Exam Unremarkable in early stages. Hepatomegaly (45%) Splenomegaly (30%) Excoriations (20%) Ascites (1%)
8 Pediatric PSC Associated more with autoimmune features (25%-28%) vs. adult (6%). Alkaline phosphatase (ALP) has wide range due bone isoenzymes induced by growth. Gamma-glutamyl transpeptidase (GGT) more reliable index of biliary injury in children.
9 Imaging Dominant stricture of biliary tree less common in children ERCP and MRCP are both safe in children with equal performance MRCP provides imaging proximal to strictures and the extra-luminal abdomen. ERCP; intervention (stent balloon dilatation), CC sampling
10 Natural course Median survival from diagnosis to OLT 9-18y. Inter-individual variability in the rate of progression Asymptomatic patients have a significantly better prognosis, 17% present with small-duct PSC Prognosis in children may be somewhat better than that of adults, since dominant strictures, recurrent cholangitis and cholangiocarcinoma are uncommon.
11 Treatment No prospective, randomized controlled trials of therapy of PSC in children Recommendations are based on studies in adults and anecdotal findings from cases series in children
12 Ursodeoxycholic acid (UDCA), Biochemical improvement Decreased pruritus Lower risk of colon cancer May reduce cholangiocarcinoma incidence May need high doses No impact on progression or survival vs mg/kg/day
13 Treatment- other Supportive; Nutritional Fat soluble vitamins, calcium Managing complications (dominant stricture, cholangitis, stones, osteoporosis) Pruritus; Cholestyramine, rifampin, naltrexone, serotonin Silymarin- improvement of LFT (pilot not RCT) Immunosuppressants in overlap
14 Oral Vancomycin Davies et al. JPGN 2008
15 MSH experience 47 patients. Mean age at diagnosis 11 +/- 4.9 years 62% male Most diagnosed based on liver biopsy and MRCP Miloh et al. Clin Gastro & Hepatol 2009
16 MSH experience 2 Co-morbidities 12% 23% 16% 33% 16% UC Crohn AIH IBD+AIH none
17 MSH experience 3 Fibrosis on liver biopsy 9% 56% 35% Stage 1-2 Stage 3 Stage 4
18 MSH experience 4 Laboratory findings U/L diagnosis After UDCA 0 GGT ALP ALT AST
19 MSH experience 5 Liver transplantation was performed in 8/47 (17%) 63% were female. Median time from diagnosis to liver transplantation : 7 years (range 4-19 years). 7/8 had fibrosis stage 3-4 on diagnosis. None had documented SC recurrence to date.
20 MSH experience 6 Most pediatric SC patients were: Symptomatic at diagnosis. Had either IBD, overlap, or both. IBD may be quiescent or develop after OLT. Liver enzymes improved on UDCA but effect on outcome remains unclear.
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